The interaction of the tumor cell with its extracellular matrix may play an important role in determining its metastatic and invasive properties. We have identified, isolated, characterized, and cloned three nonintegrin laminin binding proteins that are present in both normal and neoplastic tissues. All three proteins bind to the poly-N- acetyllactosamine carbohydrate structures on laminin. The 67 kDa high affinity laminin receptor (67LR) is expressed to a greater degree in metastatic tissues than in benign conditions in a variety of tissue- specific neoplasms. The 67LR is synthesized from a cytoplasmic precursor (37LRP) with an approximate molecular mass of 37 kDa. It is not clear how the precursor is converted into the 67LR. Epitope- tagging experiments indicate that the 37LRP is modified through a 55 kDa intermediate. The 37LRP contains a laminin binding site as well as a binding site for the Sindbis virus receptor. The two other nonintegrin laminin binding proteins have recently been renamed galectin-1 and galectin-3. They have molecular masses of 14 kDa and 31 kDa, respectively. Expression of galectin-3 varies in different tissues. In colorectal and breast carcinomas, galectin-3 is down- regulated, and its expression is inverse to that of the 67LR. However, in thyroid tissues, galectin-3 is not expressed in normal or benign conditions, but is present in several thyroid neoplasms. Future studies will determine if the selective use of different laminin binding proteins by cancer cells may play a functional role in the disease process.